As survival has improved for the 2 million people with cardiorespiratory failure managed annually in US intensive care units (ICUs), it has become apparent that these patients suffer from severe and persistent post-discharge symptoms of psychological distress including depression, anxiety, and post- traumatic stress disorder (PTSD). However, few targeted interventions exist that are relevant to patients' experiences and that accommodate their many physical, social, and financial barriers to personalized care. To fill this gap, we developed an innovative app-based mobile mindfulness training program that promotes automated care delivery and self-management of symptom-related distress. Subsequently, we conducted a pilot randomized clinical trial (RCT) called the LIFT study (R34 AT00819) that compared mobile mindfulness to both a standard telephone mindfulness program and an ICU education control among survivors of cardiorespiratory failure. We found that mobile mindfulness was feasibly delivered, acceptable, usable, and had a greater clinical impact on psychological distress than either comparator. This trial also highlighted opportunities to improve the intervention's impact related to its targeted population, content delivery, and system technology. To address these gaps, we propose a 5-year project that is conceptualized as the Optimization Phase of a multiphase optimization study (MOST) framework. We will optimize mobile mindfulness with four specific aims: (1) Optimize the usability of key technological elements of mobile mindfulness; (2) Using a factorial experimental design, identify which intervention components contribute most meaningfully to feasibility, usability, and impact on psychological distress; (3) Explore barriers and facilitators to intervention implementation; and (4) Using a mixed methods approach and data from Aims 2 & 3, refine, update, and operationalize the final mMT intervention system. At the conclusion of this U01 involving 320 cardiorespiratory failure survivors, we will deliver a mobile mindfulness system fully optimized for usability, efficiency, scalability, and clinical impact that will be off-the-shelf ready for a next-step definitive RCT?and can serve as a model for distance-based mind and body interventions. Innovative elements of our U01 proposal include its paradigm-shifting automated stepped therapy approach and its easily disseminatable mobile app delivery system?attributes that could allow seamless, inexpensive population-level scaling of mMT and other mind-body therapies. This study addresses research priorities on distress symptoms, personalized precision medicine, and self- management outlined by the National Institutes of Health and numerous professional societies. Our proven research network has the experience to conduct this U01 project that could advance the field with a personalizable therapy that fills an important clinical care gap for a growing population.